Lyme disease, which affects both children and adults, is caused by the tickborne spirochete, Borrelia burgdorferi. The illness usually begins with a characteristic skin lesion, erythema migrans, and may be followed by myocarditis, meningitis, cranial neuritis, radiculoneuritis, or arthritis. Years later, patients may develop chronic arthritis, encephalopathy/polyneuropathy, or acrodermatitis. Diagnosis has been complicated by the lack of specificity of serologic testing, and treatment failure has occurred at each stage of the illness. The work in this grant covers the clinical manifestations, diagnosis, and treatment of this complex, multisystem disorder. During the next granting period, in studies pertaining to the clinical description of the disorder, the type and frequency of late manifestations of Lyme disease will be determined by the long-term followup of patients entered into our previous studies of this illness. The late, chronic neurologic manifestations of Lyme disease will be detailed; diagnostic criteria will be developed for these manifestations of the illness; and immunogenetic profiles will be determined in these patients. The post Lyme disease syndrome will be described. In treatment studies, the efficacy of intravenous treatment regimens will be determined for chronic neurologic manifestations of Lyme disease. The efficacy of oral antibiotic regimens for children and adults with Lyme arthritis will be ascertained, and the role of host factors will be determined among those who fail to respond. The efficacy of doxycycline, amoxicillin/probenecid, and azithromycin will be compared for the treatment of early Lyme disease. In an effort to improve diagnosis, criteria for seropositivity by Western blotting will be determined for each stage of the illness. A B. burgdorferi expression library will be made in an effort to produce a group or recombinant proteins that are specific for this infection. Finally, a T-cell proliferative assay, Western blotting, and an immune complex assay will be tested for their diagnostic value in patients who are seronegative by ELISA. This work will help to solve the current problem areas in the diagnosis and treatment of Lyme disease.